X-chromosome inactivation and selection in somatic cells

Area of Science:

• Developmental Biology
• Genetics
• Cell Biology

Background:

• X-chromosome inactivation in mammalian females creates mosaic somatic cell populations, with either maternal or paternal X active.
• Heterozygosity for cell-autonomous X-linked traits provides natural cellular markers for studying development and selection.

Purpose of the Study:

• To investigate developmental phenomena, specifically cell selection, using mosaicism in X-linked heterozygotes.
• To determine if somatic cell selection is a normal aspect of mammalian development.

Main Methods:

• Utilizing individuals heterozygous for cell-autonomous X-linked traits as a model system.
• Analyzing tissue mosaic composition to detect significant shifts from the expected 1:1 ratio of maternal to paternal X-chromosome activity.
• The system is designed to detect selection acting on both X-linked loci and newly arisen autosomal variants.

Main Results:

• In the absence of selection, tissues are expected to exhibit a mosaic composition approaching a 1:1 ratio.
• Significant deviations from the 1:1 mosaicism indicate the presence of somatic cell selection.
• Several instances of somatic cell selection were identified using this methodology.

Conclusions:

• The described system effectively detects selection acting on X-linked and autosomal loci during somatic development.
• Somatic cell selection, as investigated here, is concluded not to be a typical feature of mammalian ontogeny.